Keely Cheslack-Postava

Closely Spaced Pregnancies Are Associated With Increased Odds of Autism in California Sibling Births

OBJECTIVE: To determine whether the interpregnancy interval (IPI) is associated with the risk of autism in subsequent births. METHODS: Pairs of first- and second-born singleton full siblings were identified from all California births that occurred from 1992 to 2002 using birth records, and autism diagnoses were identified by using linked records of the California Department of Developmental Services. IPI was calculated as the time interval between birth dates minus the gestational age of the second sibling. In the primary analysis, logistic regression models were used to determine whether odds of autism in second-born children varied according to IPI. To address potential confounding by unmeasured family-level factors, a case-sibling control analysis determined whether affected sibling (first versus second) varied with IPI. RESULTS: An inverse association between IPI and odds of autism among 662 730 second-born children was observed. In particular, IPIs of <12, 12 to 23, and 24 to 35 months were associated with odds ratios (95% confidence intervals) for autism of 3.39 (3.00–3.82), 1.86 (1.65–2.10), and 1.26 (1.10–1.45) relative to IPIs of ≥36 months. The association was not mediated by preterm birth or low birth weight and persisted across categories of sociodemographic characteristics, with some attenuation in the oldest and youngest parents. Second-born children were at increased risk of autism relative to their firstborn siblings only in pairs with short IPIs. CONCLUSIONS: These results suggest that children born after shorter intervals between pregnancies are at increased risk of developing autism; the highest risk was associated with pregnancies spaced <1 year apart.

Cohort effects explain the increase in autism diagnosis among children born from 1992 to 2003 in California

BACKGROUND The incidence and prevalence of autism have dramatically increased over the last 20 years. Decomposition of autism incidence rates into age, period and cohort effects disentangle underlying domains of causal factors linked to time trends. We estimate an age-period-cohort effect model for autism diagnostic incidence overall and by level of functioning. METHODS Data are drawn from sequential cohorts of all 6 501 262 individuals born in California from 1992 to 2003. Autism diagnoses from 1994 to 2005 were ascertained from the California Department of Development Services Client Development and Evaluation Report. RESULTS Compared with those born in 1992, each successively younger cohort has significantly higher odds of an autism diagnosis than the previous cohort, controlling for age and period effects. For example, individuals born in 2003 have 16.6 times the odds of an autism diagnosis compared with those born in 1992 [95% confidence interval (CI) 7.8-35.3]. The cohort effect observed in these data is stronger for high than for low-functioning children with an autism diagnosis. DISCUSSION Autism incidence in California exhibits a robust and linear positive cohort effect that is stronger among high-functioning children with an autism diagnosis. This finding indicates that the primary drivers of the increases in autism diagnoses must be factors that: (i) have increased linearly year-to-year; (ii) aggregate in birth cohorts; and (iii) are stronger among children with higher levels of functioning.

Association of Hormonal Contraceptive Use With Reduced Levels of Depressive Symptoms: A National Study of Sexually Active Women in the United States

An estimated 80% of sexually active young women in the United States use hormonal contraceptives during their reproductive years. Associations between hormonal contraceptive use and mood disturbances remain understudied, despite the hypothesis that estrogen and progesterone play a role in mood problems. In this study, we used data from 6,654 sexually active nonpregnant women across 4 waves of the National Longitudinal Study of Adolescent Health (1994-2008), focusing on women aged 25-34 years. Women were asked about hormonal contraceptive use in the context of a current sexual partnership; thus, contraceptive users were compared with other sexually active women who were using either nonhormonal contraception or no contraception. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale. At ages 25-34 years, hormonal contraceptive users had lower mean levels of concurrent depressive symptoms (β = -1.04, 95% confidence interval: -1.73, -0.35) and were less likely to report a past-year suicide attempt (odds ratio = 0.37, 95% confidence interval: 0.14, 0.95) than women using low-efficacy contraception or no contraception, in models adjusted for propensity scores for hormonal contraceptive use. Longitudinal analyses indicated that associations between hormonal contraception and depressive symptoms were stable. Hormonal contraception may reduce levels of depressive symptoms among young women. Systematic investigation of exogenous hormones as a potential preventive factor in psychiatric epidemiology is warranted.

Maternal serum persistent organic pollutants in the Finnish Prenatal Study of Autism: A pilot study

Recent research emphasizes the contribution of environmental as well as genetic factors to the etiology of autism but studies testing associations between chemical exposures and autism have been limited. Prenatal exposure to persistent organic pollutants (POPs) has previously been associated with decrements in cognitive and developmental performance. We conducted a pilot study in the Finnish Prenatal Study of Autism (FiPS-A). Seventy-five cases with autism and 75 controls matched on sex, birth year, urbanization and maternal age were sampled from first-born children in the Finnish Maternity Cohort, which includes over 1million births. The study sample included births occurring from 1991 to 2000. Subjects were followed up for autism through 2007. DDT, DDE, PCB-118, PCB-138, PCB-153, PCB-156, PCB-170, PCB-180, hexachlorobenzene, and BDE-47 were measured in archived maternal serum samples taken during pregnancy using gas chromatography-high resolution mass spectrometry. Correlations between pollutant measures were assessed and mechanistically-related weighting schemes for summarizing PCB levels were compared. Case and control differences were assessed using graphical and statistical methods. All analytes, with the exception of DDT and BDE-47, were detected above the limit of quantification in all samples. The correlation between levels of individual PCB congeners and weighted summary measures was high (0.71-1.00). Paired t-tests revealed no significant differences between cases and controls for log-transformed mean values of any analyte; however, in an adjusted model the odds ratios for autism were 1.91 (p=0.29) and 1.79 (p=0.36) respectively, for subjects with total PCBs and DDE above the 90th percentile of control values. Levels of prenatal PCB exposure in FIPS-A were similar to the levels which previously correlated with poorer neurodevelopmental measures in other populations. Further study in a larger sample will be required to fully determine whether exposure to high POP levels is associated with autism diagnosis in the population.

Maternal thyroid autoantibody and elevated risk of autism in a national birth cohort

OBJECTIVE Autoimmune disruption may contribute to risk for autism; however, since previous studies relied upon clinical diagnoses, exposure misclassification and recall bias are limitations. Thyroid peroxidase antibody (TPO-Ab) is an autoantibody involved in autoimmune thyroiditis. We aimed to test the a priori hypothesis that positivity to maternal serum TPO-Ab (TPO-Ab+) (defined as >156 IU/ml) during pregnancy is related to childhood autism. METHOD The study was based on a nested case-control design of the Finnish Prenatal Study of Autism (FiPS-A), a national birth cohort that includes prospectively drawn archived maternal serum specimens from virtually the entire pregnant population of Finland beginning in 1983. Cases of childhood autism (ICD-10F84.0) born from 1987 to 2005 were ascertained by performing linkages between national birth and inpatient/outpatient registries. All diagnosed cases in Finland over the birth years, and comparison subjects without ASD or severe/profound intellectual disability were matched 1:1 on date of birth, sex, birthplace, and residence in Finland. Maternal serum specimens were assayed in 967 matched case-control pairs for TPO-Ab by a chemiluminescent microparticle immunoassay blind to case/control status. Data were analyzed by conditional logistic regression for matched sets. RESULTS The prevalence of maternal TPO-Ab+ was significantly increased in pregnancies giving rise to autism cases (6.15%) compared to controls (3.54%). The odds of autism were increased by nearly 80% among offspring of mothers who were TPO-Ab+ during pregnancy (OR=1.78, 95% CI=1.16-2.75, p=0.009), compared to mothers negative for this autoantibody. There was also a significant relationship between maternal TPO-Ab defined as a continuous variable and odds of autism (OR=1.09, 95% CI=1.01, 1.17, p=0.02). Measures of maternal thyroid hormones did not differ between groups. CONCLUSIONS These findings provide the first biomarker-based evidence that a class of known maternal autoimmune disorders is related to autism in offspring.

Association of Selective Serotonin Reuptake Inhibitor Exposure During Pregnancy With Speech, Scholastic, and Motor Disorders in Offspring

Importance Speech/language, scholastic, and motor disorders are common in children. It is unknown whether exposure to selective serotonin reuptake inhibitors (SSRIs) during pregnancy influences susceptibility to these disorders. Objective To examine whether SSRI exposure during pregnancy is associated with speech/language, scholastic, and motor disorders in offspring up to early adolescence. Design, Setting, and Participants This prospective birth cohort study examined national population-based register data in Finland from 1996 to 2010. The sampling frame includes 845 345 pregnant women and their singleton offspring with data on maternal use of antidepressants and depression-related psychiatric disorders during pregnancy. Exposures There were 3 groups of offspring: 15 596 were in the SSRI-exposed group, ie, had mothers diagnosed as having depression-related psychiatric disorders with a history of purchasing SSRIs during pregnancy; 9537 were in the unmedicated group, ie, had mothers diagnosed as having depression-related psychiatric disorders without a history of purchasing SSRIs during pregnancy; and 31 207 were in the unexposed group, ie, had mothers without a psychiatric diagnosis or a history of purchasing SSRIs. Main Outcomes and Measures Cumulative incidence of speech/language, scholastic, or motor disorders (829, 187, and 285 instances, respectively) from birth to 14 years. All hypotheses tested were formulated before data collection. Results Of the 56 340 infants included in the final cohort, 28 684 (50.9%) were male and 48 782 (86.6%) were 9 years or younger. The mean (SD) ages of children at diagnosis were 4.43 (1.67), 3.55 (2.67), and 7.73 (2.38) for speech/language, scholastic, and motor disorders, respectively. Offspring of mothers who purchased SSRIs at least twice during pregnancy had a significant 37% increased risk of speech/language disorders compared with offspring in the unmedicated group. The cumulative hazard of speech/language disorders was 0.0087 in the SSRI-exposed group vs 0.0061 in the unmedicated group (hazard ratio, 1.37; 95% CI, 1.11-1.70; P = .004). There was a significantly increased risk of these disorders in offspring in the SSRI-exposed and unmedicated groups compared with offspring in the unexposed group. For scholastic and motor disorders, there were no differences between offspring in the SSRI-exposed group and in the unmedicated group. Conclusions and Relevance Exposure to SSRIs during pregnancy was associated with an increased risk of speech/language disorders. This finding may have implications for understanding associations between SSRIs and child development.

Risk of Psychiatric and Neurodevelopmental Disorders Among Siblings of Probands With Autism Spectrum Disorders

IMPORTANCE Previous research has focused on examining the familial clustering of schizophrenia, bipolar disorder, and autism spectrum disorders (ASD). Little is known about the clustering of other psychiatric and neurodevelopmental disorders among siblings of persons with ASD. OBJECTIVE To examine the risk for psychiatric and neurodevelopmental disorders among full siblings of probands with ASD. DESIGN, SETTING, AND PARTICIPANTS The Finnish Prenatal Study of Autism and Autism Spectrum Disorders used a population-based cohort that included children born from January 1, 1987, to December 31, 2005, who received a diagnosis of ASD by December 31, 2007. Each case was individually matched to 4 control participants by sex and date and place of birth. The siblings of the cases and controls were born from January 1, 1977, to December 31, 2005, and received a diagnosis from January 1, 1987, to December 31, 2009. This nested case-control study included 3578 cases with ASD with 6022 full siblings and 11 775 controls with 22 127 siblings from Finnish national registers. Data were analyzed from March 6, 2014, to February 12, 2016. MAIN OUTCOMES AND MEASURES The adjusted risk ratio (RR) for psychiatric and neurodevelopmental disorders among siblings of probands with ASD vs siblings of matched controls. Additional analyses were conducted separately for ASD subgroups, including childhood autism, Asperger syndrome, and pervasive developmental disorders not otherwise specified. Analyses were further stratified by sex and intellectual disability among the probands. RESULTS Among the 3578 cases with ASD (2841 boys [79.4%]) and 11 775 controls (9345 boys [79.4%]), 1319 cases (36.9%) and 2052 controls (17.4%) had at least 1 sibling diagnosed with any psychiatric or neurodevelopmental disorder (adjusted RR, 2.5; 95% CI, 2.3-2.6). The largest associations were observed for childhood-onset disorders (1061 cases [29.7%] vs 1362 controls [11.6%]; adjusted RR, 3.0; 95% CI, 2.8-3.3), including ASD (374 cases [10.5%] vs 125 controls [1.1%]; adjusted RR, 11.8; 95% CI, 9.4-14.7), tic disorders (28 cases [0.8%] vs 24 controls [0.2%]; adjusted RR, 4.3; 95% CI, 2.3-8.2), attention-deficit/hyperactivity disorder (189 cases [5.3%] vs 180 controls [1.5%]; adjusted RR, 3.7; 95% CI, 2.9-4.7), learning and coordination disorders (563 cases [15.7%] vs 697 controls [5.9%]; adjusted RR, 3.2; 95% CI, 2.8-3.6), intellectual disability (104 cases [2.9%] vs 137 controls [1.2%]; adjusted RR, 3.1; 95% CI, 2.3-4.2), conduct and oppositional disorders (180 cases [5.0%] vs 221 controls [1.9%]; adjusted RR, 2.8; 95% CI, 2.2-3.5), and emotional disorders with onset specific to childhood (126 cases [3.5%] vs 157 controls [1.3%]; adjusted RR, 2.6; 95% CI, 1.9-3.4). Autism spectrum disorders were also associated with schizophrenia spectrum disorders, affective disorders, anxiety disorders, and other neurotic and personality disorders among siblings. CONCLUSIONS AND RELEVANCE Psychiatric and neurodevelopmental disorders cluster among siblings of probands with ASD. For etiologic research, these findings provide further evidence that several psychiatric and neurodevelopmental disorders have common risk factors.

The risk of childhood autism among second-generation migrants in Finland: a case-control study

BackgroundStudying second-generation immigrants can help in identifying genetic or environmental risk factors for childhood autism. Most previous studies have focused on maternal region of birth and showed inconsistent results. No previous study has been conducted in Finland.MethodsThe study was a nested case–control study based on a national birth cohort. Children born in 1987–2005 and diagnosed with childhood autism by the year 2007 were identified from the Finnish Hospital Discharge Register. Controls were selected from the Finnish Medical Birth Register. Information on maternal and paternal country of birth and mother tongue was collected from the Finnish Central Population Register. There were 1132 cases and 4515 matched controls. The statistical test used was conditional logistic regression analysis.ResultsCompared with children with two Finnish parents, the risk of childhood autism was increased for those whose parents are both immigrants (adjusted odds ratio [aOR] 1.8, 95% confidence interval [CI] 1.2–2.7) and for those with only an immigrant mother (aOR 1.8, 95% CI 1.2–2.7), but not for those with only an immigrant father. The risk was increased for those with a mother born in the former Soviet Union or Yugoslavia and for those with a mother or a father born in Asia. Specific parental countries of birth associated with an increased risk were the former Soviet Union, the former Yugoslavia and Vietnam.ConclusionsIn Finland, children who are born to immigrant mothers with or without an immigrant partner, have an increased risk of childhood autism. The risk varies with immigrant parents’ region of birth. The findings may help in identifying possible risk factors, which can be examined in future studies.

Variation by Diagnostic Subtype in Risk for Autism Spectrum Disorders Associated with Maternal Parity among Finnish Births

BACKGROUND Associations between maternal parity and outcomes in offspring may provide evidence for involvement of prenatal exposures. The objective of this study was to determine whether risk for autism spectrum disorders (ASD) is associated with maternal parity. METHODS Diagnoses of childhood autism, Asperger syndrome, and pervasive developmental disorder, not otherwise specified (PDD-NOS) were examined separately and as a group. The study was conducted in the Finnish Prenatal Study of Autism, which is based in a national birth cohort. Children born in Finland in 1987-2005 and diagnosed with ASD by 2007 were identified through the Finnish Hospital Discharge Register. Four matched controls were selected for each case using the Finnish Medical Birth Register. The association between parity and each ASD was determined using conditional logistic regression and adjusted for number of children in the sibship and other potential confounders. RESULTS ASDs combined showed a pattern of decreasing risk with increasing parity (odds ratio OR for fourth or greater vs. first-born children, 0.43 [95% confidence interval (CI): 0.35, 0.51]). For childhood autism, an adjusted OR of 1.51 [95% CI 1.27, 1.81] was observed for second vs. first-born children. Associations for Asperger syndrome and PDD-NOS were consistent with those for all ASDs. CONCLUSIONS Differences in patterns of association between maternal parity and ASD subtypes may indicate varying contributions of specific environmental factors to risk; however, differences in diagnosis or in treatment seeking for childhood behavioural problems cannot be ruled out, particularly for higher functioning cases.

Independent review of social and population variation in mental health could improve diagnosis in DSM revisions.

At stake in the May 2013 publication of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), are billions of dollars in insurance payments and government resources, as well as the diagnoses and treatment of millions of patients. We argue that the most recent revision process has missed social determinants of mental health disorders and their diagnosis: environmental factors triggering biological responses that manifest themselves in behavior; differing cultural perceptions about what is normal and what is abnormal behavior; and institutional pressures related to such matters as insurance reimbursements, disability benefits, and pharmaceutical marketing. In addition, the experts charged with revising the DSM lack a systematic way to take population-level variations in diagnoses into account. To address these problems, we propose the creation of an independent research review body that would monitor variations in diagnostic patterns, inform future DSM revisions, identify needed changes in mental health policy and practice, and recommend new avenues of research. Drawing on the best available knowledge, the review body would make possible more precise and equitable psychiatric diagnoses and interventions.